Central nervous system (CNS) disorders, such as Alzheimer's Disease (AD), Parkinsin's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Leukodystrophies, affect millions of people worldwide and most of CNS diseases currently have no cure. Transplantation of neural cells has been demonstrated in non-human primates and rodents to be a very promising therapeutic strategy for treating CNS disorders. However, cell therapy requires high quality and large quantities of primary neural cells that are not readily obtainable. Different methods have been developed during last two decades to produce neural cells in vitro. These technologies include generation of neural cells from human embryonic stem cells (hESC), from induced human pluripotent stem cells (hiPSC), and from direct conversion of somatic cells. There are several limitations to existing art. For example, neural cells derived from hESC encounter the safety issue due to potential tumorgenesis caused by residual hESC in the differentiated products as well as immune rejection issue due to allogeneic transplantation. hiPSC can be obtained from specific patients and thus alleviate the immunorejection issue, but like hESC, it still encounters the safety issue.
Recently, the field of direct somatic lineage conversion has attracted much attention. In 2010, Wernig's group first demonstrated that a set of transcription factors can convert fibroblasts into neurons. Several laboratories have used various neural factors and microRNAs to generate fibroblast-neuron conversion. Very recently, it was reported that over-expression transcription factors can mediate reprogramming of mouse fibroblasts to myelinogenic OPCs. Thus, direct fibroblast-OPC conversion provides an alternative, potentially complementary, tool to many of the proposed applications of hESC/hiPSC technology for both disease modeling and development of cell-based therapies. Direct conversion or reprogramming has a number of advantages, including: the time required to generate, expand and differentiate pluripotent cells is avoided, and the postmitotic state of induced neural cells has a much lower risk of cancer and teratoma formation. Therefore, neural cells derived from direct conversion of fibroblasts have been favored for autologous transplantation. However, all reports on direct conversion of somatic cells into neural cells have been using transcription factors, which often involve lengthy conversion procedure and are regarded not safe due to integration of viral vector sequence into the genome.